Liver cancer displaying biliary phenotype (LCB) includes types of liver cancer that have several degrees of biliary epithelial differentiation such as intrahepatic cholangiocarcinoma and combined hepatocellular cholangiocarcinoma. Among liver cancers, the type showing a biliary phenotype is the second most prevalent, with or without chronic hepatitis, and is more aggressive than hepatocellular carcinoma (HCC), the main form of primary liver cancer.

The researchers conducted whole genomic sequencing on 30 liver tumors, classified as LCB, and compared their findings with 60 of the more common hepatocellular carcinoma tumors. For the purpose of understanding gene expression, the researchers then analyzed RNA sequencing data from 25 of the biliary-phenotype cancers and 44 hepatocellular cancers. Notably, they discovered that despite the disparity in gene expression between the two types of liver cancer, the general pattern of mutations were the same among patients with either hepatitis B or C, compared to the variations seen in the patients without a co-infection.

According to Hidewaki Nakagawa of the RIKEN Center for Integrative Medical Sciences, who led the team, “This is an interesting finding and could indicate that the cancers–even of different histological types–in patients with hepatitis infections could be derived from similar cells, perhaps hepatic progenitor cells. In patients without hepatitis, we did not find any clustering, and this indicates that their cancers might have a very different cellular origin.”

This study showed a high influence of chronic hepatitis on the genome-wide mutational patterns in liver cancer and in the genetic diversity among LCBs. Dr. Nakagawa said, “Through our analysis, we were able to identify some liver cancers with biliary phenotype that are closer to liver cancer, and others that are similar to bile duct cancer. We hope that this will in the future allow us to create therapies tailored for each type. We also hope that the new mutations we discovered could be used as targets for future therapeutics.”

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